Inotropic effect of adrenomedullin in the isolated perfused rat heart

Szokodi, István; Kinnunen, Pentti; Ruskoaho, Heikki

doi:10.1046/j.1365-201x.1996.454169000.x

Cited by 67 publications

(46 citation statements)

References 7 publications

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“…20 These results suggest that AM may participate in both short-and long-term regulation of hemodynamic function. The renal response to long-term AM administration in experimental HF included a sustained natriuresis and rise in creatinine clearance, as well a tendency for urine output and cAMP excretion to be elevated.…”

Section: Chronic Effects Of Adrenomedullin In Sheep With Experimentalmentioning

confidence: 83%

Long-Term Adrenomedullin Administration in Experimental Heart Failure

et al. 2002

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Abstract-Short-term administration of adrenomedullin, a recently discovered peptide with potent vasodilator, natriuretic, and aldosterone-inhibitory actions, has beneficial effects in experimental and clinical heart failure. The effects of prolonged adrenomedullin administration have not previously been assessed in this setting. Consequently, in 16 sheep with pacing-induced heart failure, we infused either adrenomedullin (10 ng/kg per minute; nϭ8) or a vehicle control (Hemaccel; nϭ8) for 4 days. Compared with control data, infusion of adrenomedullin persistently increased circulating levels of the peptide (by Ϸ9.5 pmol/L; PϽ0.001), in association with prompt (15 minutes) and sustained (4 days) increases in cardiac output (day 4, 27%), and reductions in peripheral resistance (30%), mean arterial pressure (13%), and left atrial pressure (24%; all, PϽ0.001). Adrenomedullin also significantly enhanced urinary sodium excretion (day 4, 3-fold; PϽ0.05), creatinine excretion (1.2-fold; PϽ0.001), and creatinine clearance (1.4-fold; PϽ0.001) over the 4 days of treatment, whereas urine volume and cAMP excretion tended to be elevated (both, 0.1ϾPϾ0.05). Plasma renin activity was increased (PϽ0.05), whereas aldosterone levels were reduced in a sustained fashion (PϽ0.01). Plasma endothelin rose transiently (hours 1 to 6) after initiation of treatment (PϽ0.05). Despite substantial cardiac unloading, plasma concentrations of the natriuretic peptides were not significantly different from control. In conclusion, long-term administration of adrenomedullin induces pronounced and sustained cardiovascular and renal effects in experimental heart failure, including reductions in cardiac preload and afterload, as well as augmentation of cardiac output, sodium excretion, and glomerular filtration. These findings support the concept of adrenomedullin as a protective hormone during hemodynamic compromise with therapeutic potential in heart failure.

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Section: Chronic Effects Of Adrenomedullin In Sheep With Experimentalmentioning

confidence: 83%

Long-Term Adrenomedullin Administration in Experimental Heart Failure

et al. 2002

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“…Moreover, this positive inotropic effect of AM is inhibited by CGRP , a CGRP receptor antagonist (37). However, the effects of the two peptides on the heart are not quite similar: although CGRP also has a positive chronotropic effect, no chronotropic action of AM has been observed in either anesthetized rats (38) or isolated perfused rat hearts (35). Thus, the vasodilator peptides AM and CGRP might exhibit a cardioprotective effect through slightly different mechanisms.…”

Section: Discussionmentioning

confidence: 93%

“…Thus, AM may exert a cardioprotective effect as shown in CGRP (33,34). In addition, both AM (35) and CGRP (36) have been shown to exhibit a positive inotropic action. Moreover, this positive inotropic effect of AM is inhibited by CGRP , a CGRP receptor antagonist (37).…”

Section: Discussionmentioning

confidence: 99%

Regional Hemodynamic Effects of Adrenomedullin in Wistar Rats: A Comparison with Calcitonin Gene-Related Peptide.

et al. 2002

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“…A direct negative inotropic effect was demonstrated in isolated hearts (Perret et al, 1993) and also in rabbit isolated myocytes (Ikenouchi et al, 1997). In contrast, positive inotropic actions have been reported (Szokodi et al, 1996;Ihara et al, 2000), whereas other authors have found no effect of ADM on myocardial contractility (Stangl et al, 2000). Studies in intact conscious sheep have shown that ADM increases the heart rate (HR), maximum rate of change in aortic flow (an index of contractility), cardiac output (CO), coronary blood flow (CBF) and coronary conductance (CC) (Parkes, 1995).…”

Section: Introductionmentioning

confidence: 91%

Direct coronary vasodilator action of adrenomedullin is mediated by nitric oxide

Matteo

May

2003

British J Pharmacology

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1 Increased circulating levels of adrenomedullin (ADM) cause peripheral vasodilatation and hypotension, accompanied by cardiac actions including tachycardia and increases in cardiac contractility, cardiac output, coronary conductance (CC) and coronary blood flow (CBF). It is unclear to what extent these cardiac effects are direct actions of ADM or secondary to the hypotension and altered cardiac loading. 2 The direct cardiac actions of ADM were examined in conscious sheep previously implanted with aortic and coronary flow probes, and an indwelling left coronary artery cannula. Responses to infusion of ADM (0.5 mg kg À1 h À1 for 1 h) into the left coronary artery or jugular vein were compared (n ¼ 6). The effect of blockade of nitric oxide (NO) synthase with intracoronary (i.c.)), infused for 2 h before and during ADM infusion, was assessed to determine whether the responses to ADM were mediated by NO (n ¼ 5). 3 I.c. ADM caused large and sustained increases in CC (0.3570.07 -0.5570.13 ml min À1 mmHg À1 , Po0.05) and CBF (2876-4279 ml min À1 , Po0.05), but had no effect on arterial pressure or indices of cardiac contractility (first differential of the upstroke of systole and peak aortic flow rate). Intravenous infusion of ADM had no effects. 4 I.c. L-NNA, at a dose that abolished the coronary vasodilator action of acetylcholine, blocked ADM-induced coronary vasodilatation. 5 In conclusion, ADM had a direct coronary vasodilator action that was mediated by release of endogenous NO and resulted in increased CBF. There was no evidence for a direct inotropic action of ADM.

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Inotropic effect of adrenomedullin in the isolated perfused rat heart

Cited by 67 publications

References 7 publications

Long-Term Adrenomedullin Administration in Experimental Heart Failure

Long-Term Adrenomedullin Administration in Experimental Heart Failure

Regional Hemodynamic Effects of Adrenomedullin in Wistar Rats: A Comparison with Calcitonin Gene-Related Peptide.

Direct coronary vasodilator action of adrenomedullin is mediated by nitric oxide

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